CDK control pathways integrate cell size and ploidy information to control cell division.

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Cell size homeostasis is crucial for eukaryotic cell function.
• Cell division must be coordinated with cell growth to maintain size.
• Cyclin-dependent kinase (CDK) activity is central to regulating mitosis and cell size.

Purpose of the Study:

• To investigate how cell size information is processed by the cell cycle network in fission yeast.
• To dissect the in vivo determinants of CDK activity related to cell size.

Main Methods:

• Development of a high-throughput single-cell assay for CDK activity in vivo.
• Analysis of CDK inhibitory phosphorylation and the role of phosphatase PP2A.
• Comparison of CDK activity in haploid and diploid cells.

Main Results:

• Inhibitory tyrosine phosphorylation of CDK encodes cell size information.
• The phosphatase PP2A contributes to setting a division size threshold.
• Diploid cells show reduced CDK activity compared to haploid cells of equivalent size, indicating DNA-dependent inhibition.

Conclusions:

• CDK inhibitory phosphorylation and PP2A act synergistically to prevent premature mitosis in smaller cells.
• DNA levels can inhibit CDK activity, further contributing to cell size homeostasis.
• Multiple mechanisms, including cyclin-CDK scaling, phosphorylation, PP2A, and DNA-dependent inhibition, regulate cell size in fission yeast.